Neurodevelopment in Urban Environments: Role of Exposure to Ambient Air Pollution

描述(由申请人提供)：美国城市中不断增长的儿童人口暴露在城市环境中的各种神经毒素中，这些毒素可能会损害他们发育中的大脑。在过去的十年里，环境健康科学家已经产生了令人信服的数据，关于暴露在道路交通排放(或交通空气污染[TAP])的当今空气污染物中的动物和人类的神经毒性，包括城市环境中的颗粒物和臭氧。实验动物模型已经证明，生命早期暴露于这些城市空气污染物会导致记忆障碍和长期的神经行为变化。与神经毒理学文献一致的是，先前来自横断面和纵向流行病学研究的数据显示，与学龄或更小的儿童接触TAP有关的广泛不良神经认知影响(包括低智商)。然而，目前尚不清楚TAP介导的不良神经认知效应是否会持续到晚年，可能会影响青少年的学习成绩和教育成就。尽管毒物学家已经揭示了空气污染导致前额叶和海马区神经毒性的明确证据，但流行病学研究尚未将较高的皮质控制功能(例如执行功能[EFS]；情绪调节)作为不利暴露对神经发育影响的神经心理调节因子。以前的研究只提供了很少的关于暴露于城市儿童通常经历的神经毒性水龙头和社会应激源所导致的联合逆境的可能性的见解。为了解决这些知识差距，这项应用的主要目标是：(1)产生关于城市环境中神经发育的计划长期研究所需的初步数据和基础设施；以及(2)开发一个概念性框架，以阐明导致认知障碍的神经心理途径和暴露于城市空气污染物中的长期社会经济后果。具体地说，我们建议进行一项纵向研究，基于正在进行的(2000年后)和特征良好的南加州城市居住双胞胎队列(R01MH058354)，包括从学龄儿童(9-10岁)到年轻人(19-23岁)的神经心理功能和结果评估的综合数据。这一应用利用了正在进行的儿童健康研究中独特的、前瞻性收集的环境数据和资源，从而能够估计早年(1990年以后)暴露在空气污染中的情况，并详细描述青少年期间城市内水龙头暴露的特征。从心理健康研究中的两个理论模型(认知易损性-应激反应和情绪失调)出发，我们将检验这一假说，即EFS/情绪调节及其发展轨迹既是TAP暴露对认知能力和社会经济成就后续不利影响的中心靶点和神经心理学中介。该项目的成功实施可能会极大地推动城市环境中发展神经科学的新兴领域。

DESCRIPTION (provided by applicant): The growing population of children in American cities is exposed to various neurotoxins present in urban environments which may damage their developing brains. Over the last decade, environmental health scientists have generated compelling data on neurotoxicity in animals and humans exposed to present-day air pollutants from road traffic emissions (or traffic air pollution [TAP]), including particulate matter and ozon in urban environments. Experimental animal models have demonstrated that early life exposures to these urban air pollutants result in memory impairment and long-term neurobehavioral changes. Consistent with neurotoxicological literature, previous data from both cross-sectional and longitudinal epidemiologic studies showed a wide range of adverse neurocognitive effects (including low IQ) associated with TAP exposure in school-aged or younger children. However, it remains unclear whether TAP-mediated adverse neurocognitive effects persist into later life possibly affecting academic performance and educational attainment in adolescents and young adults. Although toxicologists have revealed clear evidence of air pollution-induced neurotoxicity in the prefrontal lobe and hippocampus, epidemiologic studies have not yet examined higher cortical control functions (e.g., executive functions [EFs]; emotion regulation) as neuropsychological mediators of the adverse exposure-effects on neurodevelopment. Previous studies only provided very little insight on the likelihood of joint adversities resulting from exposures to both neurotoxic TAP and social stressors commonly experienced by urban-dwelling children. To address these knowledge gaps, the primary objectives of this application are to: (1) generate preliminary data and infrastructure needed for a planned long-term study on neurodevelopment in urban environments; and (2) develop a conceptual framework to elucidate neuropsychological pathways contributing to impaired cognition and long-term socioeconomic consequences of exposures to urban air pollutants. Specifically, we propose a longitudinal study built on an ongoing (2000- onwards) and well-characterized urban-dwelling Southern California Twin Cohort (R01MH058354) with comprehensive data on neuropsychological functions and outcomes assessed from school-age (aged 9-10) to young adults (aged 19-23). This application leverages the unique, prospectively-collected environmental data and resources of the ongoing Children's Health Study, enabling the estimation of early life (1990-onward) exposure to air pollution and detailed characterization of intra-urban TAP exposure during adolescents. Drawing from two theoretical models (cognitive vulnerability-stress response and emotional dysregulation) in mental health research, we will test the hypothesis that EFs/emotion regulation and their developmental trajectories serve as both the central target and neuropsychological mediators of subsequent adverse effects of TAP exposure on cognitive abilities and socioeconomic attainment. The successful performance of this project may greatly advance the emerging field of developmental neurosciences in urban environments.